EP0130739A2
Expired / Lapsed
EP
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Reactor system and method for polynucleotide synthesis
Assignee: Novartis Vaccines and Diagnostics Inc
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Filing: 1984-06-20
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Granted: —
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Expires: 2004-06-20
Abstract
Abstract A reactor system and method for synthesizing or degrading polynucleotides and other linear polymers includes a tubular reactor (12) connected to a reagent manifold (14). The polynucleotide is immobilized on a loosely packed solid-phase support material in the tubular reactor (12), and reagents are sequentially introduced into the tubular reactor. After each reagent is introduced, the tubular reactor is isolated from the reagent manifold (14) and the reagent agitated by alternatively pressurizing the opposite ends of the tubular reactor. The method provides rapid and efficient synthesis of polynucleotides. By connecting two or more tubular reactors (12) to the reagent manifold (14), a plurality of polynucleotides having different sequences may be synthesized simultaneously.
Inventors
- 👤 Mickey S. Urdea
- 👤 Brian D. Warner
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-24 15:58
CPC Classifications
C; C07; C07H; C07H21/00; B; B01; B01J; B01J19/00; B01J19/0046; B01J2219/00; B01J2219/00274; B01J2219/00277; B01J2219/00279; B01J2219/00281; B01J2219/00286; B01J2219/00351; B01J2219/00389; B01J2219/00497; B01J2219/005; B01J2219/00583; B01J2219/0059; B01J2219/00596; B01J2219/0068; B01J2219/00686; B01J2219/00718; B01J2219/0072; B01J2219/00722; C40; C40B; C40B40/00; C40B40/04; C40B40/06; C40B60/00; C40B60/14; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/582; Y10; Y10S; Y10S435/00; Y10S435/82
Claims Analysis
Total Claims: 28
Claim 1
Independent Claim
85 words
A reactor system for the sequential modification of a linear polymer attached to a dispersed solid-phase support, comprising a reactor zone for holding the dispersed solid-phase support, the reactor zone having at least two access ports defined by porous barriers, a reagent manifold for selectively delivering a particular reagent to the reactor zone through at least one of said porous barriers, means for isolating the reactor zone from the reagent manifold, and means for inducing a continuously reversing flow of reagent through the reactor zone.
Claim 2
Dependent Claim
85 words
A reactor system for the sequential modification of a linear polymer attached to a dispersed solid-phase support, comprising a reactor zone for holding the dispersed solid-phase support, the reactor zone having at least two access ports defined by porous barriers, a reagent manifold for selectively delivering a particular reagent to the reactor zone through at least one of said porous barriers, means for isolating the reactor zone from the reagent manifold, and means for inducing a continuously reversing flow of reagent through the reactor zone.
Claim 3
Dependent Claim
104 words
A reactor system for the sequential modification of two or more linear polymers attached to dispersed solid-phase support, comprising, a plurality of reactor zones for holding the dispersed solid-phase supports, the reactor zones having at least two access ports defined by porous barriers, a reagent manifold for selectively delivering particular reagents to each reactor zone one at a time through said porous barriers, means for selectively blocking the flow of reagents to the reactor zones from the reagent manifold, and means for selectively inducing a continuously reversing flow of reagent through each reactor zone when the flow of reagents to that reactor is blocked.
Claim 4
Dependent Claim
104 words
A reactor system for the sequential modification of two or more linear polymers attached to dispersed solid-phase support, comprising, a plurality of reactor zones for holding the dispersed solid-phase supports, the reactor zones having at least two access ports defined by porous barriers, a reagent manifold for selectively delivering particular reagents to each reactor zone one at a time through said porous barriers, means for selectively blocking the flow of reagents to the reactor zones from the reagent manifold, and means for selectively inducing a continuously reversing flow of reagent through each reactor zone when the flow of reagents to that reactor is blocked.
Claim 5
Dependent Claim
41 words
A reactor system as claimed in either Claim 1 or 2, wherein the reactor zone is defined by an elongate tubular column which is open at both ends, said open ends defining the access ports and having the porous barriers thereacross.
Claim 6
Dependent Claim
28 words
A reactor system as claimed in any preceding claim, further including a surge volume between the means for isolating or blocking and the ends of the reactor zone.
Claim 7
Dependent Claim
43 words
A reactor system as claimed in any preceding claim, wherein the means for inducing a continuously reversing flow of reagents includes means for supplying a pressurized inert gas and means for directing the pressurized inert gas alternately to both of said access ports.
Claim 8
Dependent Claim
35 words
A reactor system as claimed in Claim 5, wherein the means for directing said pressurized inert gas comprises a three-way valve intermediate the inert gas supply means and each access port of the reactor zone.
Claim 9
Dependent Claim
40 words
A reactor system as claimed in any preceding claim, wherein the means for isolating or blocking includes first and second isolation valves selectively capable of (a) directing reagents to the reactor, (b) pressurizing the reactor, and (c) venting the reactor.
Claim 10
Dependent Claim
43 words
A reactor system as claimed in Claim 6, wherein the means for isolating and means for inducing further include surge volume between each isolation valve and the reactor zone, said surge volume being at least equal to the volume of the reactor zone.
Claim 11
Dependent Claim
30 words
A reactor system as claimed in any preceding claim, wherein the means for blocking or isolating includes first and second isolation valves capable of selectively directing reagents to each reactor.
Claim 12
Dependent Claim
138 words
A reator system for the sequential modification of,a linear polymer attached to a dispersed solid-phase support, comprising a tubular reactor for holding the solid-phase support, the reactor being enclosed at each end by a porous barrier, a plurality of reagent reservoirs and wash reservoirs, at least some of the reagent and wash reservoirs being arranged in pairs, a reagent manifold having a plurality of entry ports for receiving reagents and wash solutions from the reservoirs, and at least one outlet for directing the reagents and wash solutions to the reactor, wherein said pairs of reagents and wash solutions each enter the manifold through common entry ports, and means for isolating the reactor from the reagent manifold and for alternately pressurizing the two opposite ends of the reactor to induce a reversing flow of reagents or wash solutions therethrough.
Claim 13
Dependent Claim
138 words
A reator system for the sequential modification of,a linear polymer attached to a dispersed solid-phase support, comprising a tubular reactor for holding the solid-phase support, the reactor being enclosed at each end by a porous barrier, a plurality of reagent reservoirs and wash reservoirs, at least some of the reagent and wash reservoirs being arranged in pairs, a reagent manifold having a plurality of entry ports for receiving reagents and wash solutions from the reservoirs, and at least one outlet for directing the reagents and wash solutions to the reactor, wherein said pairs of reagents and wash solutions each enter the manifold through common entry ports, and means for isolating the reactor from the reagent manifold and for alternately pressurizing the two opposite ends of the reactor to induce a reversing flow of reagents or wash solutions therethrough.
Claim 14
Dependent Claim
149 words
A reactor system for the sequential modification of two or more linear polymers attached to dispersed solid-phase supports, comprising a plurality of tubular reactors for holding the solid-phase supports, the reactors being enclosed at each end by a porous barrier, a plurality of reagent reservoirs and wash reservoirs, at least some of the reagent and wash reservoirs being arranged in pairs, a reagent manifold having a plurality of entry ports for receiving reagents and wash solutions from the reservoirs, and at least one outlet for directing the reagents and wash solutions to the reactors, wherein said pairs of reagents and wash solutions each enter the manifold through common entry ports, means for selectively blocking each reactor from the reagent manifold, and means for alternatively pressurizing the two opposite ends of each reactor to induce a reversing flow of reagents or wash solutions therethrough when the reagent manifold is blocked.
Claim 15
Dependent Claim
149 words
A reactor system for the sequential modification of two or more linear polymers attached to dispersed solid-phase supports, comprising a plurality of tubular reactors for holding the solid-phase supports, the reactors being enclosed at each end by a porous barrier, a plurality of reagent reservoirs and wash reservoirs, at least some of the reagent and wash reservoirs being arranged in pairs, a reagent manifold having a plurality of entry ports for receiving reagents and wash solutions from the reservoirs, and at least one outlet for directing the reagents and wash solutions to the reactors, wherein said pairs of reagents and wash solutions each enter the manifold through common entry ports, means for selectively blocking each reactor from the reagent manifold, and means for alternatively pressurizing the two opposite ends of each reactor to induce a reversing flow of reagents or wash solutions therethrough when the reagent manifold is blocked.
Claim 16
Dependent Claim
40 words
A reactor system as claimed in either Claim 10 or 11, wherein the pairs of reagents and wash solutions are connected to their respective entry ports through common valves to assure that the reagent is completely washed from the manifold.
Claim 17
Dependent Claim
25 words
A reactor system as claimed in Claim 12, wherein each reagent and wash solution pair is connected to the manifold through two valves in series.
Claim 18
Dependent Claim
46 words
A reactor system as claimed in Claim 13, wherein the two valves in series include a two-way common port valve connected to the entry port in the reagent manifold and a three-way valve connected to selectively direct either reagent or wash s.olution to the two-way valve.
Claim 19
Dependent Claim
36 words
A reactor system as claimed in Claims 10 to 14, wherein the reagent and wash reservoirs are capable of being pressurized to induce flow of reagent and wash solutions through the manifold to the reactor zone.
Claim 20
Dependent Claim
33 words
A reactor system as claimed in Claim 15, further including means for selectively pressurizing the reagents and wash reservoirs to deliver reagent and wash solutions to the reactor zone through the reagent manifold.
Claim 21
Dependent Claim
26 words
A reactor system as claimed in Claim 16, wherein the pressurizing means further includes means for isolating the reservoirs from each other to prevent cross contamination.
Claim 22
Dependent Claim
51 words
A reactor system as claimed in any one of Claims 10 to 17, further comprising a control system for selectively directing reagent and wash solutions to the reactor zone, isolating or blocking the reactor zone, and pressurizing the reactor zone to induce a reversing flow of reagents or wash solutions therethrough.
Claim 23
Independent Claim
63 words
A method for synthesizing polynucleotides by selectively introducing reagents to a solid-phase substrate in a tubular reactor zone whereby individual nucleotides are sequentially added to a chain of nucleotides attached to said substrate, said method characterized by retaining at least some of the reagents within the reactor zone and inducing an oscillating flow of reagents by alternately pressurizing each side of the reactor.
Claim 24
Independent Claim
63 words
A method for synthesizing polynucleotides by selectively introducing reagents to a solid-phase substrate in a tubular reactor zone whereby individual nucleotides are sequentially added to a chain of nucleotides attached to said substrate, said method characterized by retaining at least some of the reagents within the reactor zone and inducing an oscillating flow of reagents by alternately pressurizing each side of the reactor.
Claim 25
Independent Claim
76 words
A method for simultaneously synthesizing two or more polynucleotides by selectively introducing reagents to a plurality of solid-phase substrates, each substrate being contained in a tubular reactor zone, whereby individual nucleotides are sequentially added to a chain of nucleotides attached to each of said substrates, said method characaterized by retaining at least some of the reagents within each reactor zone and simultaneously inducing an oscillating flow of reagents by alternately pressurizing both sides of each reactor.
Claim 26
Independent Claim
76 words
A method for simultaneously synthesizing two or more polynucleotides by selectively introducing reagents to a plurality of solid-phase substrates, each substrate being contained in a tubular reactor zone, whereby individual nucleotides are sequentially added to a chain of nucleotides attached to each of said substrates, said method characaterized by retaining at least some of the reagents within each reactor zone and simultaneously inducing an oscillating flow of reagents by alternately pressurizing both sides of each reactor.
Claim 27
Dependent Claim
27 words
A method for synthesizing polynucleotides as claimed in either Claim 19 or 20, wherein the flow of reactants is reversed at a frequency from 1 to 10hz.
Claim 28
Independent Claim
35 words
A method for synthesizing polynucleotides as claimed in any one of Claims 19 to 21, wherein the oscillating flow of reagents is induced by alternately pressurizing each side of the reactor, with an inert gas.
References Cited (Backward Citations)
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